[摘要]：Heme acts as a ligand for transcription factors and regulates the expression of several genes. The nuclear receptor retinoid X receptor alpha (RXR alpha) plays important roles in various nuclear receptor-dependent signaling pathways. We here show that heme binds to RXR alpha and impairs its DNA-binding activity. Deletion and mutation studies of RXR alpha revealed that the binding region of hemin corresponded to the ligand binding domain of mouse RML and cysteine 374 was involved in the binding. The DNA-binding activity using the DR-1 consensus sequence of RXR alpha in electrophoretic mobility shift assays was inhibited by heme. The reporter assay also showed a decrease of RXR alpha-dependent transcriptional activity. It was reported that hemin enhanced the adipocyte differentiation of mouse 3T3-L1 cells, where the functions of several nuclear receptors including RXR alpha and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) are activated. However, the inductions of adipogenic factor mRNAs including PPAR-gamma, fatty acid binding protein-4 and glucose transporter-4 were markedly repressed by heme during adipocyte differentiation. These results suggest that heme causes the impairment of RXRa-dependent signal pathways and inhibits the adipocyte differentiation of 3T3-L1 cells. (c) 2008 Elsevier B.V. All rights reserved.
